A hypothesis linking sodium and lithium reabsorption in the distal nephron. |
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Authors: | Klaus Thomsen David G Shirley |
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Affiliation: | Centre for Basic Psychiatric Research, Aarhus University Hospital, Skovagervej 2, DK-8240 Risskov, Denmark. klt@psykiatri.aaa.dk |
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Abstract: | BACKGROUND: A hypothesis is proposed linking Na(+) and Li(+) reabsorption in the distal nephron. The handling of these two ions in the distal nephron is related because they share the same apical membrane entry mechanism: the amiloride-sensitive Na(+) channel (ENaC). However, the two ions exit the cell through different transport mechanisms: Na(+) via the Na(+)-K(+)-ATPase and Li(+) via the Na(+)/H(+) exchanger. Studies in rats have shown that under normal circumstances hardly any Li(+) is reabsorbed in the distal nephron, so that the urinary excretion of Li(+), expressed as a fraction of the delivery to the early distal tubule (FE(Li dist)), amounts to approximately 0.97. In contrast, during severe dietary Na(+) restriction, FE(Li dist) decreases to 0.50-0.60. Our hypothesis is that the absence of distal Li(+) reabsorption during intake of a normal diet can be explained by a negative driving force for Li(+) entrance across the apical membrane in those segments in which ENaC is active. METHOD: We propose a model that incorporates this concept. RESULTS: The model indicates that the lowering of FE(Li dist) during dietary Na(+) restriction can be explained by activation of apical ENaC in extra sub-segments further downstream. In these extra sub-segments the driving force for Li(+) reabsorption is positive, leading to significant Li(+) reabsorption. During dietary K(+) restriction, FE(Li dist) is reduced to 0.35-0.55. The model shows that this reduction in FE(Li dist) can be explained by hyperpolarization of the apical membrane in ENaC-containing sub-segments, which is known to occur in this condition. CONCLUSION: We conclude that the model may improve current understanding of both Na(+) and Li(+) handling in the distal nephron. |
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Keywords: | amiloride collecting duct distal nephron epithelial sodium channel, ENaC lithium reabsorption sodium reabsorption |
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